Clinical Interests

Research Interests

Molecular basis of cortical-basal ganglia and cortical-cerebellar circuit formation and dysfunction in neurological and psychiatric disease.

Publications

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Research

Research in the Middleton lab focuses on defining substrates of normal and abnormal motor and cognitive function. This is accomplished by performing high-throughput genetic, epigenetic, and functional genomic studies involving human subjects or animal and cellular models of various neuropsychiatric, neurodegenerative, and addictive disorders. The specific disorders of most interest include autism, schizophrenia, ADHD, Parkinson's disease, alcohol abuse, and traumatic brain injury. In addition to the use of similar analytical methods to study these conditions, another common underlying theme is the attempt to define their relationship to neural-immune responses. Thus, the neural-immune axis forms a major lab interest as well, and this has been pursued through several collaborative efforts in studies of central and peripheral inflammatory and immune system alterations in these and other conditions, such as lupus, multiple sclerosis, and Zika virus infection. While in the past, it might have been nearly impossible for one lab to simultaneously pursue research on so many different topics, with the advent of modern bioinformatic tools and systems biological methods, these integrated approaches are now seen as highly valuable. Indeed, comparisons across disorders can help define the specificity of the changes that are seen and may lead to the identification of novel biomarkers or therapeutic agents. As examples, recent publications from the lab describe several novel discoveries of DNA mutations causally linked to schizophrenia, or microRNA biomarkers in peripheral blood or saliva that are strongly associated with alcohol abuse or autism spectrum disorder. Students and postdoctoral fellows who are interested in the research performed in the lab will likely become well-versed in next generation sequencing, comparative anatomical analysis, and statistical data mining.